Risk Factors for Thyroid Function Test Abnormalities During Pregnancy: A Systematic Review of the Literature to Validate Current Risk Factors and Identify Novel Ones

Background: International guidelines recommend that the indication to perform thyroid function testing during pregnancy is based on the presence of risk factors for thyroid function test abnormalities. However, the discriminative ability of currently recommended risk factors is questionable. To inform on an update of the American Thyroid Association Guidelines for the Diagnosis and Management of Thyroid Disease in Preconception, Pregnancy, and the Postpartum, we aimed to systematically review the literature to evaluate evidence for current risk factors and potential novel ones for thyroid function test abnormalities in pregnancy. Methods: A systematic literature search was performed on Embase, Medline Ovid, and the Cochrane Library from inception to October 17, 2024, to identify articles on the associations of any candidate variables with thyroid function test abnormalities, thyroid antibody positivity, or results of continuous thyroid function tests in pregnancy. Additional records were identified through citation searching. Study quality was assessed using the Newcastle-Ottawa Scale. We summarized the results using a narrative synthesis. Results: A total of 81 articles were included, describing 36 candidate variables. Thyroid antibody positivity was associated with a higher risk of overt or subclinical hypothyroidism compared with antibody negativity (absolute risks: 2.4-7.0% vs. 0.1-0.2% for overt hypothyroidism and 1.9-29.0% vs. 2.0-5.7% for subclinical hypothyroidism). In cases of iodine deficiency, sufficiency, and intake above pregnancy requirements or excess, the absolute risks for subclinical hypothyroidism were 2.2-42.6%, 1.42-16.0%, and 3.8-24.3%, respectively. A limited number of studies were available for history of autoimmune diseases, family history of thyroid disease, symptoms of hypothyroidism, and history of pregnancy loss, preterm delivery, or infertility. There was little or no association of current risk factors with isolated hypothyroxinemia or (subclinical) hyperthyroidism. We did not identify novel risk factors for thyroid function test abnormalities. Conclusions: Evidence for most currently recommended risk factors remains limited and heterogeneous, and no novel risk factor was identified. While risk factors can help guide thyroid function testing in pregnancy, a clinical risk assessment cannot be replaced. Future studies are needed to detect novel risk factors that can improve the accuracy and efficiency of identifying pregnant women at high risk of thyroid function test abnormalities, in particular, overt hypothyroidism.